Systems and methods for a thermal cycler heated cover

ABSTRACT

A thermal cycler system for use with a sample holder configured to receive a plurality of samples includes a sample block configured to receive the sample holder, a cover lid configured to move in a direction toward the sample block from an open position to a closed position, a heated cover operatively coupled to the cover lid and configured to move in a direction toward the sample block from a raised position to a first lowered position, in which the heated cover contacts the sample holder when the sample holder is received by the sample block, and a drive assembly including a motion guide configured to move in a direction toward the sample block from a first position, wherein the cover lid is in the open position and the heated cover is in the raised position, to a second position, wherein the cover lid is in the closed position.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.15/387,631, filed Dec. 21, 2016, which claims the benefit under 35U.S.C. § 119(e) of U.S. Provisional Patent Application No. 62/270,695filed on Dec. 22, 2015 (Now expired), which is hereby incorporated byreference in their entirety.

TECHNICAL FIELD

The present invention relates generally to thermal cycler systems andmethods of using same.

BACKGROUND

Testing of biological or chemical samples often requires a device forrepeatedly subjecting multiple samples though a series of temperaturecycles. To prepare, observe, test, and/or analyze an array of biologicalsamples, one example of an instrument that may be utilized is a thermalcycler or thermocycling device, such as an end-point polymerase chainreaction (PCR) instrument or a quantitative, or real-time, PCRinstrument. Such devices are used to generate specific temperaturecycles, i.e. to set predetermined temperatures in the reaction vesselsto be maintained for predetermined intervals of time.

Generally, it is desirable to increase the efficiency and output of thePCR process. Advances in automated biological sample processinginstruments allow for quicker and more efficient analysis of samples.However, such automated systems often must be capable of integratingwith other automated laboratory systems. Eliminating user interactionincreases efficiency but requires the development of feedback controlsto cue the main instrument controller that the next stage in the processis ready to occur. For example, the system must be sure that a sampleholder is in place within the biological analysis system beforeactivating the thermal cycling routine. In an automated system wherethere are no user interventions, it is desirable to cue the maininstrument controller that the sample holder is in place based onfeedback by the lab automation system.

A potential method to detect that the consumer plate in position is theuse of an imaging system integrated into the main lab automation system.The imaging system may capture an image and, through complex algorithms,determine the presence of a sample holder on the sample block of the PCRsystem. Such a method is complex, costly, and tedious to implement.Other methods include the embedding of a sensitive load cell on thesample block module or the use of a barcode reader, which can detect thepresence of the plate through a weight change or a barcode on the sampleholder, respectively. However, such methods are costly to implement.

There is an increasing need to provide improved thermal cycler systemsthat address one or more of the above drawbacks.

SUMMARY

In accordance with one embodiment, a thermal cycler system for use witha sample holder configured to receive a plurality of samples includes asample block configured to receive the sample holder, a cover lid, aheated cover operatively coupled to the cover lid, and a drive assemblyfor moving the cover lid and the heated cover. The cover lid isconfigured to move in a direction toward the sample block from an openposition to a closed position. The heated cover is configured to move ina direction toward the sample block from a raised position to a firstlowered position, in which the heated cover contacts the sample holderwhen the sample holder is received by the sample block. The driveassembly includes a motion guide operatively coupled to the cover lidand to the heated cover. The motion guide is configured to move in adirection toward the sample block from a first position, wherein thecover lid is in the open position and the heated cover is in the raisedposition, to a second position, wherein the cover lid is in the closedposition.

In accordance with another embodiment, a thermal cycler system for usewith a sample holder configured to receive a plurality of samplesincludes a sample block configured to receive the sample holder, aheated cover, and a first sensor. The heated cover is configured to movein a direction toward the sample block from a raised position to a firstlowered position, wherein the heated cover is in contact with the sampleholder when the sample holder is received by the sample block, and fromthe first lowered position to a second lowered position when the sampleholder is removed from the sample block, wherein the heated cover is incontact with the sample block. The first sensor is configured to detectwhether the heated cover is in the first lowered position.

Various additional features and advantages of the invention will becomemore apparent to those of ordinary skill in the art upon review of thefollowing detailed description of the illustrative embodiments taken inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate embodiments of the invention and,together with a general description of the invention given above, andthe detailed description given below, serve to explain the invention.

FIG. 1 is a perspective view of a thermal cycler system according to oneembodiment showing the cover lid in an open position.

FIG. 2 is a perspective view of the thermal cycler system of FIG. 1showing the cover lid in a closed position.

FIG. 3 is a front perspective view of the thermal cycler system of FIG.1 with an outer housing removed.

FIG. 4 is a rear perspective view of the thermal cycler system of FIG. 1with the outer housing removed.

FIGS. 5A-5D are rear perspective views of a portion of the thermalcycler system of FIG. 1 showing a cover lid, a motion guide, and aheated cover in various positions.

FIGS. 6A-6C are cross-sectional views of a portion of the thermal cyclersystem taken generally along line 6B-6B of FIG. 5C showing the heatedcover in various positions relative to a sample holder positioned on thesample block.

FIG. 7 is a cross-sectional view of a portion of the thermal cyclersystem taken generally along line 7-7 of FIG. 5D showing the heatedcover positioned on the sample block without a sample holder.

FIG. 8 is a cross-sectional view of a portion of the thermal cyclersystem taken generally along line 8-8 of FIG. 4 showing the guides.

DETAILED DESCRIPTION

Referring to FIGS. 1-4, a thermal cycler system 10 is shown constructedin accordance with an illustrative embodiment of the present invention.The thermal cycler system 10 includes an outer housing 12 and a sampleblock 14 configured to receive a sample holder 16. The sample block 14includes a plurality of cavities 18 and is configured to be loaded withthe correspondingly shaped sample holder 16 containing a plurality ofbiological or biochemical samples located in a plurality of wells 20, asshown best in FIG. 8. The thermal cycler system 10 further includes aheated cover or platen 22 operatively coupled to a pressure bar 24(shown in FIG. 5A) and a cover lid 26. The heated cover 22 is configuredto provide a downward force to the sample holder 16. The downward forceprovides vertical compression between the sample holder 16, sample block14, and the other components of a thermal block assembly (not shown),which improves thermal contact between the sample block 14 and thesample holder 16 to heat and cool the samples in the wells 20. As shownin FIGS. 3 and 4, the thermal cycler system 10 also includes a driveassembly 28 for moving the cover lid 26 from an open position (FIG. 1)to a closed position (FIG. 2) and for moving the heated cover 22 from araised position (FIG. 6A) to a lowered position (FIGS. 6C and 7). Thedrive assembly 28 includes a belt drive system 30 and a motion guide 32.The thermal cycler system 10 further includes a sensor assembly forsensing various positions of the heated cover 22 and the motion guide 32as described in greater detail below.

The thermal cycler system 10, unless otherwise indicated, is describedherein in the exemplary embodiment using a reference frame in which thesample block 14 is located in the front or forward portion of thethermal cycler system 10, the belt drive system 30 is located in theback or rearward portion of the thermal cycler system 10, and the coverlid 26 is located above the sample block 14 when the cover lid 26 is inthe closed position. Consequently, as used herein, terms such asforward, backward, downward, upward, lateral, and vertical used todescribe the exemplary thermal cycler system 10 are relative to thechosen reference frame. The embodiments of the present invention,however, are not limited to the chosen reference frame and descriptiveterms. For example, the belt drive system 30 may be located in the frontor forward portion of the thermal cycler system 10 and be within thescope of the invention. Those of ordinary skill in the art willrecognize that the descriptive terms used herein may not directly applywhen there is a change in reference frame. Nevertheless, the relativeterms used to describe embodiments of the thermal cycler system 10 areto merely provide a clear description of the exemplary embodiments inthe drawings. As such, the relative terms forward, backward, downward,upward, lateral, and vertical are in no way limiting the presentinvention to a particular location or orientation.

With reference to FIGS. 3 and 4, the belt drive system 30 is shown inmore detail. The belt drive system 30 is configured to move the motionguide in a lateral direction forward toward the sample block 14 andbackward away from the sample block 14. The belt drive system 30includes a belt 34 looped about a pair of spaced apart pulleys 36, 38and a screw 40. The belt drive system 30 may also include an electricdrive motor and a transmission, such as a gear box, that transfersmotive power from the drive motor to the pulley 36 for moving the belt34 about the pulleys 36, 38. A first end 42 of the screw 40 is coupledto the pulley 38. As the belt 34 rotates around the pulleys 36, 38, thescrew 40 rotates. A second end 44 of the screw 40 is operatively coupledto the motion guide 32. More particularly, the second end 44 of thescrew 40 extends through a cylindrical tube 46, which is coupled to themotion guide 32 by a bracket 48. The cylindrical tube 46 includesthreads (not shown) that cooperate with threads 50 of the screw 40.Thus, as the screw 40 rotates, the engagement of threads 50 with thecorresponding threads in the tube 46 provides an axially directedsliding motion of the tube 46 and, thus, the motion guide 32 toward oraway from the sample block 14.

With reference to FIG. 5A, the heated cover 22 and the pressure bar 24are shown in more detail. The heated cover 22 is coupled to the pressurebar 24 via springs 52 a, 52 b. The springs 52 a, 52 b may be compressionsprings or die springs, for example. The dimensions of a die spring maybe smaller than a compression spring capable of handling the same load.Die springs may also have a longer service cycle and may be able towithstand high heat. A die spring may be used when higher loads need tobe taken or when higher temperatures need to be withstood. In oneembodiment, the springs 52 a, 52 b may be TL16-36 die springs availablefrom Tokyo Hatsujyo Manufacturing Co., Ltd. The pressure bar 24 isengaged with the motion guide 32, and, thus, the heated cover 22 isoperatively coupled with the motion guide 32. To that end, ends 54, 56of the pressure bar 24 include projections 62 a, 62 b, and side walls58, 60 of the motion guide 32 include slots 64 a, 64 b. The projections62 a, 62 b extend through the slots 64 a, 64 b. The slots 64 a, 64 b areslanted allowing longitudinal motion of the motion guide 32 along ahorizontal axis to translate into simultaneous vertical motion of thepressure bar 24 along a vertical axis and, consequently, the heatedcover 22. The vertical motion of the pressure bar 24 may be guided byguides 66 a, 66 b, which are described in greater detail below. When thepressure bar 24 moves in a vertical direction toward the sample block14, the springs 52 a, 52 b exert a force on the heated cover 22.Accordingly, the heated cover 22 moves in a vertical direction towardthe sample block 14 until it contacts the sample holder 16 when it isreceived by the sample block 14. When the heated cover 22 is in contactwith the sample holder 16, further downward movement is prevented. Ifthe pressure bar 24 continues to move vertically downward, the springs52 a, 52 b will compress and the heated cover 22 will exert a force onthe sample holder 16.

Referring still to FIG. 5A, the cover lid 26 and the housing 12 areshown in more detail. The housing 12 has shoulders 68 a, 68 b (shown inphantom) that engage the cover lid 26. More specifically, the cover lid26 includes ledges 70 a, 70 b that engage the undersides of theshoulders 68 a, 68 b, respectively. As the cover lid 26 moves from theopened position to the closed position, the ledges 70 a, 70 b move alongthe shoulders 68 a, 68 b. The underside of the shoulders 68 a, 68 bincludes projections 72 a, 72 b at an end of the shoulders 68 a, 68 b.When the cover lid 26 reaches the closed position, the projections 72 a,72 b prevent further movement of the cover lid 26 in a direction awayfrom the belt drive system 30.

With further reference to FIG. 5A, the cover lid 26 and the motion guide32 are shown in more detail. The cover lid 26 includes a front wall 74,opposed side walls 76, 78, and a rear wall 80. The cover lid 26 isconfigured to be moved longitudinally from the open position to theclosed position by the motion guide 32. In the illustrative embodiment,the cover lid 26 and the motion guide 32 are engaged in various manners.To that end, the rear wall 80 of the cover lid 26 is coupled to across-bar 82 of the motion guide 32 by springs 84 a, 84 b. In oneembodiment, the springs 84 a, 84 b may be compression springs, such astype SSC-028-12 coil springs available from Shincoil Spring Pte Ltd.Additionally, the cover lid 26 is engaged with the motion guide 32 viathe pressure bar 24. In that regard, the side walls 76, 78 of the coverlid 26 include vertical channels 86 a, 86 b through which the ends 54,56 of the pressure bar 24 extend. Thus, when the projections 62 a, 62 bof the pressure bar 24 move through the slots 64 a, 64 b of the motionguide 32, the ends 54, 56 of the pressure bar 24 move vertically throughthe channels 86 a, 86 b of the cover lid 26. The channels 86 a, 86 b aidthe guides 66 a, 66 b in preventing relative longitudinal motion betweenthe pressure bar 24 and the cover lid 26. The cover lid 26 furtherincludes troughs 88 a, 88 b. Each of the troughs 88 a, 88 b are shown asbeing discontinuous in the particular embodiment illustrated within FIG.5A, although the invention is not so limited. The bottoms edges of theside walls 58, 60 of the motion guide 32 are engaged in the troughs 88a, 88 b. When the motion guide 32 moves relative to the cover lid 26,the side walls 58, 60 of the motion guide 32 move through the troughs 88a, 88 b, respectively.

With reference to FIGS. 5A-5D, the operation of the drive assembly 28 isshown in detail. FIGS. 5A and 5B show the movement of the cover lid 26in a direction toward the sample block 14 from the open position to theclosed position. As shown in FIG. 5A, when the motion guide 32 is in afirst position, the cover lid 26 is in the open position and the heatedcover 22 is in a raised position. When the cover lid 26 is in the openposition, the sample holder 16 may be loaded on the sample block 14 by,for example, a robotic arm (not shown). After the sample block 14receives the sample holder 16, the belt drive system 30 may be engaged.As the belt drive system 30 rotates the screw 40, the motion guide 32moves in a direction toward the sample holder 16. The forward movementof the motion guide 32 causes the cover lid 26 to move longitudinally ina direction toward the sample holder 16 due at least in part to theengagement between the ends 54, 56 of the pressure bar 24 and thechannels 86 a, 86 b of the cover lid 26. When the cover lid 26 movesforward from the open to the closed position, the cover lid 26 and themotion guide 32 move as one unit. In other words, the relative positionsof the cover lid 26 and the motion guide 32 generally remain unchanged.With reference to FIG. 5B, the cover lid 26 is shown in a closedposition relative to the sample block 14, and the motion guide 32 isshown in a second position forward of the first position relative to thesample block 14. At this point, further movement of the cover lid 26 ina direction away from the belt drive system 30 is prevented byprojections 72 a, 72 b of the outer housing 12.

With reference to FIGS. 5C and 5D, the movement of the heated cover 22and the pressure bar 24 in a direction toward the sample block 14 fromthe raised position is shown. After the cover lid 26 reaches the closedposition and as the screw 40 continues to rotate, the motion guide 32continues to move in a longitudinal direction toward the sample block14. Because the cover lid 26 is prevented from moving further forward,the springs 84 a, 84 b compress as the space between the cross-bar 82 ofthe motion guide 32 and the rear wall 80 of the cover lid 26 decreases.Accordingly, the side walls 58, 60 and, thus, the slots 64 a, 64 b ofthe motion guide 32 move laterally along the side walls 76, 78 of thecover lid 26 of the motion guide 32 in a direction toward the sampleblock 14. Because the pressure bar 24 is laterally constrained by thechannels 86 a, 86 b of the cover lid 26, the projections 62 a, 62 b movethrough the slanted slots 64 a, 64 b. Additionally, as the motion guide32 moves relative to the cover lid 26, the side walls 58, 60 of themotion guide 32 move through the troughs 88 a, 88 b, respectively. Inone embodiment, the projections 62 a, 62 b are rotatable so that, whenthe pressure bar 24 moves relative to the motion guide 32, theprojections 62 a, 62 b rotate through the slanted slots 64 a, 64 b. Whenthe projections 62 a, 62 b move through the slanted slots 64 a, 64 b,the pressure bar 24 moves in a vertical direction toward the sampleblock 14. As shown in FIG. 5C, the heated cover 22 moves to a firstlowered position in which the heated cover 22 contacts the sample holder16 when the sample holder 16 is received by the sample block 14. Whenthe heated cover 22 is in the first lowered position, the motion guide32 is in a third position forward of the second position relative to thesample block 14. As shown in FIG. 5D, when the sample holder 16 isremoved from the sample block 14, the heated cover 22 is configured tomove to a second lowered position in which the heated cover 22 is in aposition intermediate of the first lowered position and the sample block14. When the heated cover 22 is in the second lowered position, themotion guide 32 is in a fourth position forward of the third positionrelative to the sample block 14. In the illustrated embodiment, themotion guide 32 will not move to the fourth position when the sampleholder 16 is received by the sample block 14.

Referring again to FIGS. 5A-5D, the sensor assembly is shown in detail.The sensor assembly includes a first sensor 90 and a second sensor 92.In one embodiment, the sensors 90, 92 may be deep gap slotted opticalswitches, such as type OPB820 W sensors available from OPTEK Technology.The exemplary sensors 90, 92 include two spaced apart arms 94 and areconfigured to detect when a locating pin is positioned between the arms94. The motion guide 32 includes a locating pin 96. The first sensor 90is configured to detect if the cover lid 26 is in the open position, asshown in FIG. 5A. To that end, when the cover lid 26 is in the openposition, the locating pin 96 of the motion guide 32 is located betweenthe arms 94 of the first sensor 90 so that the sensor 90 detects thepresence of the locating pin 96. The second sensor 92 is configured todetect if the cover lid 26 is closed and the sample holder 16 is removedfrom the sample block 14 (i.e., the motion guide is in the fourthposition). In such a case, when the motion guide 32 is in the fourthposition, the locating pin 96 is located between the arms 94 of thesecond sensor 92 so that the second sensor 92 detects the presence ofthe locating pin 96. When the second sensor 92 detects the presence ofthe locating pin 96, the drive system may be configured to disengagebecause the motion guide 32 is in the forward-most position (i.e., thefourth position). As discussed above, if the sample holder 16 isreceived by the sample block 14, the motion guide 32 will move to thethird position but not to the fourth position. Thus, the second sensor92 will not detect the location of the motion guide 32 if the sampleholder 16 is received by the sample block 14 because the locating pin 96will not be located within the arms 94 of the second sensor 92.

With reference to FIGS. 6A-6C and FIG. 7, the movement of the heatedcover 22 and the pressure bar 24 is shown in more detail. FIGS. 6A-6Cshow the movement of the heated cover 22 from a raised position to afirst lowered position when the sample holder 16 is received by thesample block 14. In FIG. 6A, the heated cover 22 is shown in the raisedposition. When the pressure bar 24 moves in a vertical direction towardsthe sample block 14, the heated cover 22 moves downward to the firstlowered position and contacts the sample holder 16, as shown in FIG. 6B.After the heated cover 22 contacts the sample holder 16, the sampleholder 16 prevents the heated cover 22 from moving further in adirection toward the sample block 14. Therefore, as shown in FIG. 6C,the springs 52 a, 52 b begin to compress due to the continued downwardmovement of the pressure bar 24. In this manner, the heated cover 22exerts a force on the sample holder 16. In one embodiment, the heatedcover 22 may be configured to exert a predetermined force on the sampleholder 16. When the predetermined force is reached, the drive assembly28 may be configured to stop moving the motion guide 32 and, thus, thepressure bar 24, so that the predetermined force is not exceeded. In oneembodiment, the heated cover 22 may be configured to exert a force of 96lbf on the sample holder 16. If the sample holder 16 is removed from thesample block 14, as shown in FIG. 7, the heated cover 22 moves to thesecond lowered position.

Referring again to FIGS. 6A-6C and FIG. 7, the sensor assembly furtherincludes a third sensor 98 coupled to the pressure bar 24 via an arm100. The third sensor 98 is configured to detect if the cover lid 26 isin the closed position and the sample holder 16 is received by thesample block 14. More particularly, the third sensor 98 may beconfigured to detect whether the heated cover 22 is exerting apredetermined force on the sample holder 16. When the third sensor 98detects that the heated cover 22 is exerting a predetermined force onthe sample holder 16, the thermal cycler system 10 may be configured todisengage the drive assembly 28 to prevent exceeding the predeterminedforce. In the illustrated embodiment, the thermal cycler system 10includes a flexible connector 102, as illustrated previously in FIGS.5A-5D. The flexible connector 102 may connect the heated cover 22 and,for example, the third sensor 98. In one embodiment, the flexibleconnector 102 may also connect to a printed circuit board (not shown).After the heated cover 22 is exerting a predetermined force on thesample holder 16, the thermal cycler system 10 may then proceed to thenext step of the PCR process. In the illustrated embodiment, the thirdsensor 98 is configured to detect a locating pin 104 coupled to theheated cover 22 when the pressure bar 24 and the heated cover 22 arespaced apart by a predetermined distance. The predetermined distance isbased on the predetermined force to be exerted on the sample holder 16and depends at least in part on the characteristics of the springs 52 a,52 b. In that regard, the compressed length of the springs 52 a, 52 bdepends on the pressure bar 24 and the force being exerted by the heatedcover 22. Therefore, the distance between the pressure bar 24 and theheated cover 22 when the predetermined force is being exerted on thesample holder 16 may be determined based on the characteristics of thesprings 52 a, 52 b. Accordingly, when the heated cover 22 is exertingthe predetermined force on the sample holder 16, the locating pin 104 islocated within the arms 94 of the third sensor 98 so that the sensor 92detects the presence of the locating pin 96. Consequently, as shown inFIG. 7, the pressure bar 24 and the heated cover 22 will be spaced apartby a distance greater than the predetermined distance and the locatingpin 96 is not located between the arms 94 such that the third sensor 98will not detect the presence of the locating pin 96. Therefore, thethird sensor 98 does not detect when the heated cover 22 is in thesecond lowered position. At this point, however, the second sensor 92will detect that the motion guide 32 is in the fourth position and thedrive assembly 28 may be disengaged.

Advantageously, the configuration of the sensor assembly allows for thethermal cycler system 10 to be compatible with sample holders 16 thatvary in design, such as the design of a deck 106 of the sample holder16. For example, the deck thickness of commercially available sampleholders varies. Accordingly, when the heated cover 22 is in the firstlowered position, the distance of the heated cover 22 from the sampleblock 14 may vary depending on the thickness of the particular sampleholder 16. However, the thickness of the deck 106 does not affect thedetection of the presence of the sample holder 16 because the thirdsensor 98 indirectly detects the presence of the sample holder 16 basedon the predetermined force. Thus, the heated cover 22 may be configuredto exert the same predetermined force on sample holders 16 havingvarying deck thicknesses.

With reference to FIG. 8, the guides 66 a, 66 b are shown in moredetail. The guides 66 a, 66 b are coupled to the cover lid 26. Moreparticularly, the guides 66 a, 66 b are secured in bores 108 a, 108 b ofthe cover lid 26. The guides 66 a, 66 b extend from the cover lid 26 ina direction toward the sample block 14 and into through-holes 110 a, 110b in the pressure bar 24. The guides 66 a, 66 b are slidable through thethrough-holes 110 a, 110 b. Thus, as the pressure bar 24 moves in adirection toward the sample block 14, the through-holes 110 a, 110 bslide in a downward direction along the guides 66 a, 66 b. The guides 66a, 66 b aid in preventing horizontal or lateral movement of the pressurebar 24 and, thus, the heated cover 22. Advantageously, preventinghorizontal or lateral movement of the heated cover 22 reduces potentialshear stress on the sample holder 16 that results from the heated cover22 being lowered at an angle towards the sample holder 16.

Still referring to FIG. 8, the sample block 14 and the sample holder 16are shown in more detail. As discussed above, in various embodiments,the sample block 14 may have a plurality of cavities 18 configured toreceive a plurality of correspondingly shaped wells 20 of the sampleholder 16. The wells 20 are configured to receive a plurality ofsamples, wherein the wells 20 may be sealed within the sample holder 16via a lid, cap, sealing film or other sealing mechanism between thewells 20 and the heated cover. In the illustrative embodiment, there are96 cavities 18 in the sample block 14. In such an embodiment, the sampleholder 16 may be a 96-well microtiter plate. It should be recognizedthat the sample block 14 and the sample holder 16 may have alternateconfigurations. For example, the sample holder 16 may be, but is notlimited to, any size multi-well plate, card or array including, but notlimited to, a 32-well microtiter plate, a 50-well microtiter plate, a384-well microtiter plate, a 484-well microtiter plate, a microcard, athrough-hole array, or a substantially planar holder, such as a glass orplastic slide. The wells 20 in various embodiments of a sample holder 16may include depressions, indentations, ridges, and combinations thereof,patterned in regular or irregular arrays formed on the surface of thesample holder 16. Sample or reaction volumes can also be located withinwells or indentations formed in a substrate, spots of solutiondistributed on the surface a substrate, or other types of reactionchambers or formats, such as samples or solutions located within testsites or volumes of a microfluidic system, or within or on small beadsor spheres. Samples held within the wells 20 may include one or more ofat least one target nucleic acid sequence, at least one primer, at leastone buffer, at least one nucleotide, at least one enzyme, at least onedetergent, at least one blocking agent, or at least one dye, marker,and/or probe suitable for detecting a target or reference nucleic acidsequence.

While the present invention has been illustrated by the description ofspecific embodiments thereof, and while the embodiments have beendescribed in considerable detail, it is not intended to restrict or inany way limit the scope of the appended claims to such detail. Thevarious features discussed herein may be used alone or in anycombination. Additional advantages and modifications will readily appearto those skilled in the art. The invention in its broader aspects istherefore not limited to the specific details, representative apparatusand methods and illustrative examples shown and described. Accordingly,departures may be made from such details without departing from thescope or spirit of the general inventive concept.

What is claimed is:
 1. A thermal cycler system comprising: a sampleblock comprising a sample holder receiving surface configured to receivethe sample holder; and a cover assembly moveable in a first directionparallel to the sample holder receiving surface between an open positionand a closed position relative to the sample holder receiving surface,wherein the cover assembly covers the sample holder receiving surface inthe closed position and exposes the sample holder receiving surface inthe open position, wherein the cover assembly comprises: a platenmoveable, in the closed position of the cover assembly, in a seconddirection perpendicular to the first direction between a raised positionand a lowered position relative to the sample holder receiving surface,a cover lid over the platen, the cover lid comprising a cover surfaceand opposing side walls extending from the cover surface, an actuatablelinkage coupled to and extending transversely across the platen in adirection perpendicular to the first direction, opposite ends of theactuatable linkage being received in recesses in an interior surface ofthe opposing side walls of the cover lid, the recesses oriented in thesecond direction, the opposite ends being movable along the recesses inthe second direction to move the actuatable linkage in the seconddirection between a raised position and a lowered position, and anelastically deformable member between the actuatable linkage and theplaten, the elastically deformable member arranged to exert acompressive force against the platen in the lowered position of theplaten and the actuatable linkage.
 2. The system of claim 1, wherein theplaten is configured to be heated.
 3. The system of claim 1, furthercomprising a drive assembly operably coupled to the cover assembly, thedrive assembly configured to impart a drive force on the cover assemblyin the first direction.
 4. The system of claim 3, further comprising amotion guide coupled to the cover assembly and the drive assembly, themotion guide positioned to transfer the drive force from the driveassembly to the cover assembly, the motion guide and the cover assemblymoving together over a first range of motion in the first direction inresponse to the drive force.
 5. The system of claim 4, wherein: thecover lid further comprises a rear wall located at a trailing end of thecover lid in the first range of motion of the cover assembly from theopen position to the closed position, and the motion guide comprises acrossbar parallel the rear wall.
 6. The system of claim 1, wherein theactuatable linkage comprises a bar.
 7. The system of claim 1, whereinthe actuatable linkage moves in the second direction between the raisedposition and the lowered position when the cover assembly is in theclosed position.
 8. The system of claim 1, further comprising one ormore sensors configured to detect one or both of the platen and theactuatable linkage being in the raised position and the loweredposition.
 9. A thermal cycler system comprising: a sample blockcomprising a sample holder receiving surface configured to receive thesample holder; a cover assembly moveable in a first direction parallelto the sample holder receiving surface between an open position and aclosed position relative to the sample holder receiving surface, whereinthe cover assembly covers the sample holder receiving surface in theclosed position and exposes the sample holder receiving surface in theopen position, wherein the cover assembly comprises: a platen moveable,in the closed position of the cover assembly, in a second directionperpendicular to the first direction between a raised position and alowered position relative to the sample holder receiving surface, acover lid over the platen, the cover lid comprising a cover surface andopposing side walls extending from the cover surface, an actuatablelinkage coupled to and extending transversely across the platen in adirection perpendicular to the first direction, opposite ends of theactuatable linkage being received in recesses in an interior surface ofthe opposing side walls of the cover lid, the opposite ends beingmovable along the recesses in the second direction to move theactuatable linkage in the second direction between a raised position anda lowered position, and an elastically deformable member between theactuatable linkage and the platen, the elastically deformable memberarranged to exert a compressive force against the platen in the loweredposition of the platen and the actuatable linkage; and a motion guidecoupled to the cover assembly, the motion guide configured to transfer adrive force to the cover assembly, wherein in response to the driveforce: the motion guide and the cover assembly are movable together overa first range of motion between the open position and the closedposition of the cover assembly, and in the closed position, the motionguide is movable relative to the cover assembly.
 10. The system of claim9, further comprising a stop, the cover assembly abutting against thestop in the closed position to prevent further movement of the coverassembly in the first direction in response to continued drive force.11. The system of claim 9, wherein the platen is moveable over a secondrange of motion in the second direction in response to movement of themotion guide relative to the cover assembly.
 12. The system of claim 11,wherein the actuatable linkage moves in the second direction between theraised position and the lowered position during the second range ofmotion.
 13. A thermal cycler system comprising: a sample blockcomprising a sample holder receiving surface configured to receive thesample holder; a cover assembly moveable in a first direction parallelto the sample holder receiving surface between an open position and aclosed position relative to the sample holder receiving surface, whereinthe cover assembly covers the sample holder receiving surface in theclosed position and exposes the sample holder receiving surface in theopen position, wherein the cover assembly comprises: a platen moveable,in the closed position of the cover assembly, in a second directionperpendicular to the first direction between a raised position and alowered position relative to the sample holder receiving surface, acover lid over the platen, the cover lid comprising a cover surface andopposing side walls extending from the cover surface, an actuatablelinkage coupled to and extending transversely across the platen in adirection perpendicular to the first direction, opposite ends of theactuatable linkage being received in recesses in an interior surface ofthe opposing side walls of the cover lid, the opposite ends beingmovable along the recesses in the second direction to move theactuatable linkage in the second direction between a raised position anda lowered position, and an elastically deformable member between theactuatable linkage and the platen, the elastically deformable memberarranged to exert a compressive force against the platen in the loweredposition of the platen and the actuatable linkage; and a motion guidecoupled to the cover assembly, the motion guide configured to transfer adrive force to the cover assembly, wherein the actuatable linkage iscoupled to the motion guide via a cam-slot mechanism.
 14. The system ofclaim 13, the actuatable linkage comprising protrusions at the oppositeends of the actuatable linkage, the protrusions received in respectivecam slots of the motion guide.
 15. The system of claim 14, wherein thecam slots extend in a direction oblique to the first and seconddirections.
 16. The system of claim 14, wherein the protrusions move inthe respective cam slots in a direction oblique to the first and seconddirections during movement of the actuatable linkage between the raisedposition and the lowered position.
 17. A thermal cycler systemcomprising: a sample block comprising a sample holder receiving surfaceconfigured to receive the sample holder; a cover assembly moveable in afirst direction parallel to the sample holder receiving surface betweenan open position and a closed position relative to the sample holderreceiving surface, wherein the cover assembly covers the sample holderreceiving surface in the closed position and exposes the sample holderreceiving surface in the open position, wherein the cover assemblycomprises: a platen moveable, in the closed position of the coverassembly, in a second direction perpendicular to the first directionbetween a raised position and a lowered position relative to the sampleholder receiving surface, a cover lid over the platen, the cover lidcomprising a cover surface, opposing side walls extending from the coversurface, and a rear wall located at a trailing end of the cover lidbased on movement of the cover assembly from the open position to theclosed position, an actuatable linkage coupled to and extendingtransversely across the platen in a direction perpendicular to the firstdirection, opposite ends of the actuatable linkage being received inrecesses in an interior surface of the opposing side walls of the coverlid, the opposite ends being movable along the recesses in the seconddirection to move the actuatable linkage in the second direction betweena raised position and a lowered position, and an elastically deformablemember between the actuatable linkage and the platen, the elasticallydeformable member arranged to exert a compressive force against theplaten in the lowered position of the platen and the actuatable linkage;and a motion guide coupled to the cover assembly, the motion guidecomprises a crossbar parallel to the rear wall, wherein the elasticallydeformable member is a first elastically deformable and the systemfurther comprises a second elastically deformable member, the secondelastically deformable member coupled to the rear wall and the crossbar.18. The system of claim 17, wherein the compressive force is a firstcompressive force, and the second elastically deformable member isconfigured to exert a second compressive force on the rear wall in theclosed position.
 19. A thermal cycler system comprising: a sample blockcomprising a sample holder receiving surface configured to receive thesample holder; and a cover assembly moveable in a first directionparallel to the sample holder receiving surface between an open positionand a closed position relative to the sample holder receiving surface,wherein the cover assembly covers the sample holder receiving surface inthe closed position and exposes the sample holder receiving surface inthe open position, wherein the cover assembly comprises: a platenmoveable, in the closed position of the cover assembly, in a seconddirection perpendicular to the first direction between a raised positionand a lowered position relative to the sample holder receiving surface,a cover lid over the platen, the cover lid comprising a cover surfaceand opposing side walls extending from the cover surface, an actuatablelinkage extending transversely across the platen in a directionperpendicular to the first direction, opposite ends of the actuatablelinkage being received in recesses in an interior surface of theopposing side walls of the cover lid, the opposite ends being movablealong the recesses in the second direction to move the actuatablelinkage in the second direction between a raised position and a loweredposition, and an elastically deformable member between the actuatablelinkage and the platen, the elastically deformable member arranged toexert a compressive force against the platen in the lowered position ofthe platen and the actuatable linkage, wherein: the actuatable linkagecomprises at least one through-hole extending in the second direction,and the cover lid further comprises at least one guide extending throughthe at least one through-hole configured to: slide through the at leastone through-hole in the second direction, guide movement of the platenin the second direction between the raised position and the loweredposition, and minimize movement of the actuatable linkage in the firstdirection.